Metal salts of 1,1,5,5-tetrasubstituted dithiobiurets

ABSTRACT

Disclosed are novel metal salts of 1,1,5,5-tetrasubstituted dithiobiurets of the formula ##EQU1## in which R 1 , R 2 , R 3  and R 4 , when taken independently of each other are selected from the group consisting of C 1  -C 18  alkyl, C 6  -C 12  aryl, C 3  -C 12  cycloalkyl, and these radicals substituted by at least one member of the group consisting of hydroxyl, C 1  -C 4  alkyl, C 1  -C 8  acyl, halo and nitro, and R 1  and R 2 , when taken together along with the nitrogen to which they are bonded, and R 3  and R 4  when taken together with the nitrogen to which they are bonded, are selected from the group consisting of N-morpholinyl, N-piperidyl, N-pyrrolidyl and N-aziridinyl. The compounds are useful as population control agents.

This invention is in the chemical arts. It relates to the chemistry ofthioureas and particularly of dithiobiurets.

Dithiobiurets of the formula: ##EQU2## in which R and R' are certainsubstituted amino groups, and two processes for making them aredisclosed in the U.S. Pat. No. 3,166,564, to Diveley. These compoundswhich have several useful biological properties are not very stable andtend to oxidize fairly rapidly. This is especially true of1,1,5,5-tetramethyldithiobiuret and 1,1,5,5-tetraethyldithiobiuret. Thedithiobiurets are also relatively insoluble in water.

This invention is based on the discovery that metallic ions react withthese dithiobiurets to form salts, many of which are highly stable.These metal salts have many of the same, if not more, biologicalproperties that make them useful.

In summary, this invention comprises a group of compounds which aremetal salts of 1,1,5,5-tetrasubstituted dithiobiurets of the formula:##EQU3## in which R¹, R², R³ and R⁴, when taken independently of eachother are selected from the group consisting of C₁ -C₁₈ alkyl, C₆ -C₁₂aryl, C₃ -C₁₂ cycloalkyl, and these radicals substituted by at least onemember of the group consisting of hydroxyl, C₁ -C₄ alkyl, C₁ -C₈ acyl,halo and nitro, and R¹ and R², when taken together along with thenitrogen to which they are bonded, and R³ and R⁴ when taken togetherwith the nitrogen to which they are bonded, are selected from the groupconsisting of N-morpholinyl, N-piperidyl, N-pyrrolidyl and N-aziridinyl.In some embodiments R¹, R², R³ and R⁴ are the same. In other embodimentsone or more of them are different. Examples of metals are the lightmetals, such as the alkali metals (sodium, potassium, etc.) and thealkaline earth metals (calcium, barium, etc.) and the heavy metals suchas zinc, cadmium, tin, mercury, copper, nickel, chromium, iron, silver,manganese, cobalt and the like. Examples of C₁ -C₈ alkyl are bothstraight and branched chain alkyls such as methyl, ethyl, propyl,isopropyl, n-butyl, sec-butyl, t-butyl, and the like. Examples ofC_(6-C) ₁₂ aryl include phenyl, tolyl, naphthyl, and the like. Examplesof C₃ -C₁₂ cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, and the like. Examples of C₁ -C₄ alkyl include methyl,ethyl, propyl, isopropyl, t-butyl, and the like. Examples of C₁ -C₈ acylinclude formyl, acetyl, butyryl, and the like. Specific embodiments ofhalo are fluoro, chloro, bromo and iodo. Examples of the compounds ofthis invention include: sodium salt of 1,1,5,5-tetramethyldithiobiuret;sodium salt of 1,3-bis(N-morpholino)-1,3-dithiono-2-azapropane; zinc(II) salt of 1,1,5,5-tetramethyldithiobiuret; nickel (II) salt of1,1,5,5-tetramethyldithiobiuret; tin (II) salt of1,1,5,5-tetramethyldithiobiuret; copper (I) salt of1,1,5,5-tetramethyldithiobiuret; mercury (II) salt of1,1,5,5-tetraethyldithiobiuret; nickel (II) salt of1,1,5,5-tetraethyldithiobiuret; and zinc (II) salt of1,1,5,5-tetraethyldithiobiuret.

NMR spectra, ultraviolet spectra and polarographic data indicate thatsome of the salts of this invention are ionic salts while others arechelated salts which are more commonly called chelates. In general, thelight metal salts are ionic and the heavy metal salts are chelated,although some of the salts are of intermediate character.

The ionic salts of this invention can be represented by the followingformula I: ##EQU4##

The chelated salts of this invention can be represented by the followingformula II in the case of the salts of metal in the monovalent conditionor oxidation state: ##EQU5## and by formula III in the case of metals inthe divalent condition or oxidation state: ##EQU6## In these formulasR¹, R², R³ and R⁴ are as defined above, M is a light metal selected fromthe group consisting of alkali metals and alkaline earth metals with theexception of beryllium and magnesium and M' is selected from the groupconsisting of the heavy metals, beryllium and magnesium.

In general, the light metal salts exhibit all of the properties normallyassociated with ionic salts. In general, they are crystalline solids at20-25°C. and are highly soluble in water, but relatively insoluble inorganic solvents such as hexane, benzene, methylene chloride and thelike.

In general, the heavy metal salts and the beryllium and magnesium saltsof 1,1,5,5-tetrasubstituted dithiobiurets exhibit properties typical ofchelated metal salts. Many of the chelated salts are exceptionallystable compounds. In general, they are crystalline solids at 20°-25°C.and are insoluble in water but soluble in solvents such as benzene andthe like and chloroform and the like.

The compounds of this invention when applied to plants and administeredto animals have a number of advantageous effects. Some of the compoundsdefoliate plants. Some temporarily sterilize arthropods. Some inhibitmetamorphosis of insects and acarids. Some affect the size and functionof certain glands in animals. Some temporarily sterilize animals. In thecase of egg-laying animals, some of the compounds suppress egg-layingand eggs that are laid do not hatch. Some of the compounds terminatepregnancy when administered to pregnant mammals. All of the compounds ofthis invention have one or more of these biological properties.

Each of the compounds of this invention is derived from thecorresponding dithiobiuret. Two procedures for making the correspondingdithiobiurets are disclosed in the U.S. Pat. No. 3,166,564, to Diveley.Briefly, the two procedures for preparing the dithiobiurets can beillustrated by the following reaction A: ##EQU7## and by the reaction B:##EQU8##

The dithiobiuret salts of this invention are prepared by reacting acompound of the corresponding metal with the corresponding1,1,5,5-tetrasubstituted dithiobiuret. The corresponding dithiobiuretcan be made in situ and, without isolation, reacted directly with themetal compound, or the dithiobiuret can be isolated and then reactedwith the metal compound.

Each of the ionic light metal salts of 1,1,5,5-tetrasubstituteddithiobiurets is made by reacting the dithiobiuret with thecorresponding light metal alcoholate. The reaction can be represented bythe following equation: ##EQU9##

The reaction is preferably carried out in an inert liquid reactionmedium such as, for example, methanol and the like. The temperature atwhich the reaction takes place is not critical, but the reactionproceeds more rapidly at higher temperatures. It is preferred to conductthe reaction at temperatures in the range from about 20°C. to about30°C. The reaction is generally carried out at atmospheric pressure.However, superatmospheric and subatmospheric pressures are within thebroader concepts of this invention.

Each of the heavy metal salts of 1,1,5,5-tetrasubstituted dithiobiuretsis made by reacting a salt of the heavy metal with the dithiobiuret. Thepreparation of chelated salts in the case of salts of metals in thedivalent condition or oxidation state can be illustrated by thefollowing equation: ##EQU10## where X is an anion of an acid, HX.

In the case where the metal ion is a sufficiently strong oxidizing agentto oxidize the dithiobiuret as taught in U.S. Pat. No. 3,166,564, forexample, the copper (II) ion, the reaction can be illustrated by thefollowing equation: ##EQU11## In each case the reaction of the metalsalt with the dithiobiuret preferably is carried out in an inert liquidreaction medium, for example, acetone, ethanol and the like. Thetemperature at which the reaction takes place is not critical, but thereaction proceeds more rapidly at higher temperatures. It is preferredto conduct the reaction at temperatures in the range from about 20° toabout 30°C. The reaction is generally carried out at atmosphericpressure. However, superatmospheric and subatmospheric pressures arewithin the broader concepts of this invention.

The following examples illustrate the best mode now contemplated ofcarrying out this invention, including specific embodiments. Theinvention is not limited to these specific embodiments. In theseexamples all percentages are by weight unless otherwise indicated, allparts by weight are indicated by w, all parts by volume are indicated byv and each part by weight (w) bears the same relationship to each partby volume (v) as the kilogram does to the liter.

EXAMPLE 1

This example illustrates the preparation of the zinc (II) chelate of1,1,5,5-tetramethyldithiobiuret.

A mixture of potassium thiocyanate (20.0 w) and acetone (250 v) isstirred until the potassium thiocyanate is dissolved and thendimethylthiocarbamoyl chloride (24.7 w) is added. The mixture is heatedat reflux for 20 minutes, cooled to 25°C. and anhydrous dimethylamine(9.0 w) is passed slowly into the reaction mixture with cooling so thatthe temperature is maintained at less than 30°C. during this additionand for an additional 10 minutes. The reaction mixture is then heated to40°-50°C. for 10 minutes. The mixture is cooled to 25°C. and aspiratedfor 5 minutes to remove unreacted dimethylamine. The mixture is thenfurther cooled to less than 10°C. and the potassium chloride which formsduring the reaction is removed by filtration. The potassium chloride iswashed with acetone and the wash is combined with the filtrate. Acetoneis added to the filtrate to bring the total volume up to 300 v.

This acetone solution containing 1,1,5,5-tetramethyldithiobiuret isstirred and a solution of zinc chloride (10.9 w) dissolved in distilledwater (50 v) is added dropwise. After one hour, cold distilled water(800 v) is added. Typically an oil separates which gradually solidifies.The resulting solid is then filtered, washed on the filter with waterand air-dried. The solid is triturated with warm ethanol and filtered.The resulting solid is then recrystallized twice from benzene. Typicallythe product (8.0 w) is in the form of white powder crystals which have amelting point of 202°-204°C. These crystals consist essentially of zinc(II) chelate of 1,1,5,5-tetramethyl dithiobiuret.

Typical analysis of this product shows N = 18.6%, S = 28.7% and Zn (byatomic absorption) = 14.8% and Zn (by ethylene diamine tetraacetic acidtitration) = 14.5%. The calculated analysis for the zinc (II) chelate of1,1,5,5-tetramethyldithiobiuret is N = 18.8%, S = 28.7% and Zn = 14.65%.Typically the NMR spectrum (in CDCl₃) of the product reveals a singlesharp proton signal at 3.27 ppm. which indicates that all the protonsare equivalent. The UV spectrum (in CH₂ Cl₂) has a maximum at 273 nm.(α64.5) and a minimum of 241 nm. (α49.5). Polarographic results alsoindicate that this compound is a chelated salt and not an ionic salt.

EXAMPLE 2

This example illustrates the preparation of the zinc (II) chelate of1,1,5,5-tetramethyldithiobiuret by a procedure which includes isolatingthe intermediate 1,1,5,5-tetramethyldithiobiuret.

The procedure of Example 1 is repeated until after the dimethylamineaddition and the following heating period. The reaction mixture iscooled to 25°C. and is poured into 600 v of cold water, acidified withconcentrated hydrochloric acid and twice extracted with methylenechloride. The extract is dried over sodium sulfate and the solvent isremoved on a rotary evaporator at 50°C. during 15-20 minutes. The tan,solid residue is recrystallized from 100% ethanol to give a light tancrystalline product. Residual ethanol is removed on a rotary evaporator.Typically light tan crystals melting at 113°-115°C. are obtained. Thisproduct (21.5 w) consists essentially of1,1,5,5-tetramethyldithiobiuret. The product is stored in a dark bottleunder nitrogen in a cool place until ready for use.

A portion (19.1 w) of the 1,1,5,5-tetramethyldithiobiuret product isdissolved in acetone (250 v). The solution is stirred magnetically and asolution of zinc chloride (6.15 w) dissolved in distilled water (15 v)is added dropwise. Typically after about 1.5 hours a solid begins toseparate. Stirring is discontinued after 2 hours and the reactionproceeds for an additional 12 hours. Distilled water is added slowlywith stirring. A white solid which remains undissolved is filtered andrecrystallized from benzene and then air-dried. Typically a white powder(9.5 w) having a melting point of 202°-204°C. is obtained.

EXAMPLE 3

This example illustrates the preparation of the Ni (II) chelate of1,1,5,5-tetramethyldithiobiuret.

The nickel (II) chelate of 1,1,5,5-tetramethyldithiobiuret is preparedusing the procedure described in Example 1 using nickel chloride insteadof the zinc chloride. Typically a gray purple colored solid is obtained.Elemental analysis of this product indicates N = 18.9% and S = 28.8%.The calculated analysis for Ni (II) chelate of1,1,5,5-tetramethyldithiobiuret is N = 19.15% and S = 29.2%.

EXAMPLE 4

This example illustrates the tin (II) chelate of1,1,5,5-tetramethyldithiobiuret.

The tin (II) chelate of 1,1,5,5-tetramethyldithiobiuret is prepared bythe procedure described in Example 1 using stannous chloride instead ofzinc chloride. Typically a yellow powder melting at 230°-234°C. isobtained.

EXAMPLE 5

This example illustrates the preparation of the copper (I) chelate of1,1,5,5-tetramethyldithiobiuret.

The 1,1,5,5-tetramethyldithiobiuret is prepared and isolated as inExample 2. A portion (19.1 w) of the isolated product is dissolved inacetone (250 v) and a solution of cupric chloride (5.4 w) dissolved inwater (10 v) is added dropwise to the1,1,5,5-tetramethyldithiobiuret-acetone solution. Typically a solidproduct consisting essentially of a mixture of3,5-bis(dimethylamino)-1,2,4-dithiazolium chloride and the copper (I)chelate of 1,1,5,5-tetramethyldithiobiuret starts to form immediately.The reaction is continued at room temperature for 12 hours and theseparated solid product is filtered. The solids are washed withdistilled water to separate the water-soluble dithiazolium chloride fromthe water-insoluble copper (I) chelate. After air-drying a yellow solidproduct (7.08 w) is obtained. Typically the analysis of this productshows N = 14.7% and S = 22.5%. The calculated analysis for the Cu (I)chelate 1,1,5,5-tetramethyldithiobiuret (for the dihydrate) is N = 14.5%and S = 22.2%.

EXAMPLE 6

This example illustrates the preparation of the mercury (II) chelate of1,1,5,5-tetraethyldithiobiuret.

1,1,5,5-Tetraethyldithiobiuret is prepared using the procedure ofExample 1 and the following reagents:potassium thiocyanate 10.0 wacetone125 vdiethylthiocarbamoyl chloride 15.15 wdiethylamine 7.3 w Theresulting product is not isolated and after the KCl has been removed byfiltration a solution of mercuric acetate (8.0 w) dissolved in water (50v) is added dropwise to the solution of the1,1,5,5-tetraethyldithiobiuret. A yellow solid separates and after 24hours the solid is filtered. The resulting solid is triturated withmethanol and then hexane. Typically, after air drying, a light tancrystalline solid (17.03 w) having a melting point of 109°-112°C. isobtained.

Typically the analysis of the product shows N = 12.3%, S = 18.7% and Hg= 29.3%. The calculated analysis for the mercury (II) chelate of1,1,5,5-tetraethyldithiobiuret is N = 12.2%, S = 18.5% and Hg = 29.0%.

EXAMPLE 7

This example illustrates the preparation of the nickel (II) chelate of1,1,5,5-tetraethyldithiobiuret.

An acetone solution of 1,1,5,5-tetraethyldithiobiuret is generated insitu as described in Example 6. A solution of nickel (II) acetate (8.8w) dissolved in water (100 v) is added dropwise to the solution.Typically after air drying, a dull purple colored powder which melts at156°-157°C. is isolated. The product is soluble in benzene and insolublein water.

The analysis of this solid product is N = 15.4%, S = 24.0% and Ni =10.1%. The calculated analysis for the Ni (II) chelate of1,1,5,5-tetraethyldithiobiuret is N = 15.2%, S = 23.2% and Ni = 10.7%.

EXAMPLE 8

This example illustrates the preparation of the zinc (II) chelate of1,1,5,5-tetraethyldithiobiuret.

The procedure described in Example 6 is repeated using zinc (II) acetateand an in situ generated acetone solution of1,1,5,5-tetraethyldithiobiuret. The solid product is purified byrecrystallization from 100% ethanol. Typically an off-white crystallineproduct is obtained having a melting point of 115°-118°C.

The analysis of this product is N = 15.0%, S = 22.9% and Zn = 10.7%. Thecalculated analysis for the Zn (II) chelate of1,1,5,5-tetraethyldithiobiuret is N = 15.1%, S = 23.0% and Zn = 11.7%.

EXAMPLE 9

This example illustrates the preparation of the sodium salt of1,1,5,5-tetramethyldithiobiuret.

A solution of sodium methoxide in methanol is prepared by diluting 25%NaOCH₃ (54.0 w) in methanol with methanol (250 v).1,1,5,5-Tetramethyldithiobiuret (48.0 w) is added in portions while thesolution is stirred. The stirring is continued for 30 minutes. Thesolvent is removed on a rotary evaporator at 50°C. The residue, whichtypically is a tan solid, is stirred with CH₂ Cl₂ (100 v) to removeunreacted dithiobiuret. The solvent is removed by drying on a rotaryevaporator. Typically a water-soluble white powder (44.7 g.) having amelting point of 219°-221°C. is obtained.

An aqueous solution of this product is acidified by the addition ofconcentrated HCl. Typically a white solid is obtained having a meltingpoint identical to that of the starting 1,1,5,5-tetramethyldithiobiuret.The infrared spectrum of the acidification product also indicates that1,1,5,5-tetramethyldithiobiuret is regenerated.

To a solution of the original product (4.26 w) in water (25.0 v) isadded a solution of zinc chloride (1.0 w) in water (5 v). A white solidproduct is obtained having properties identical to the product ofExample 1.

EXAMPLE 10

This example illustrates the preparation of the sodium salt of1,3-bis(N-morpholino)-1,3-dithiono-2-azapropane.

A solution of sodium methoxide in methanol is prepared by diluting 25%NaOCH₃ (13.4 w) in methanol with methanol (100 v).1,3-bis(N-morpholino)-1,3-dithiono-2-azapropane (17.4 w) is added to thesolution in small portions. Additional methanol (75 v) is added toobtain a solution. After 15 minutes the solution is filtered andmethanol is removed from the filtrate using a rotary evaporator. Theresidue is stirred with dichloromethane (75 v) for 10 minutes. Theresulting mixture is filtered and the solid product is dried using arotary evaporator. Typically a light tan product (20.6 w) having amelting point of 205°-210°C. is obtained.

As stated above, the metal derivatives of 1,1,5,5-tetrasubstituteddithiobiurets of this invention are biologically active compounds. Someof the varied biological activities of these compounds are illustratedby the following test data. The most important, advantageous biologicalactivity of these compounds appears to be their activity as a populationcontrol agent for insects, acarids, animals and humans. The expression"population control agent" is used herein to mean an agent that inhibitsreproduction in treated members of the population. When applied tomammals the expression includes contraception agents and pregnancyterminators. In the case of insects it refers to chemosterilants andmetamorphosis inhibitors that prevent maturation of the insect into theadult stage. Certain of the compounds of this invention are animalcontraceptives which are effective when either the male or female istreated for a period of time prior to mating. The compounds have otheruseful biological properties. When orally administered to male mammalsthe compounds of this invention inhibit the growth of, or reduce thesize of, the prostate gland. Thus, they can be used in treatingprostatic hypertrophy.

Evaluation as Animal Contraceptives

The zinc (II) chelate of 1,1,5,5-tetramethyldithiobiuret was evaluatedas an animal contraceptive by the treatment of male and/or female ratsprior to mating. Separate unmated female and/or male rats were fed adiet to which had been added the test compound at 1-5 mg./kg. dosagelevels for seven days before mating. After the 7-day test period theanimals were cohabitated to mate. After mating, the females wereseparated and observed through a period of time equal to the normalgestation period for rats. Their litters were compared with that of acontrol group of animals who had the same diet but without the zinc (II)chelate of 1,1,5,5-tetramethyldithiobiuret. At the dosage levels of 1-5mg./kg. no pregnancies resulted.

Evaluation as Animal Pregnancy Terminators

Pregnant rats were treated with the test compounds at selected times andconcentrations during the gestation period. After treatment, the animalswere observed for abortions and were sacrificed and examined for thenumber and normality of their implants. The zinc (II), tin (II) andcopper (I) chelates of 1,1,5,5-tetramethyldithiobiuret were evaluated inthese tests. At a dosage level of 1-5 mg/kg. the zinc (II) chelateresulted in complete resorption of the embryos or abortion of thefetuses, depending upon what time during the gestation period treatmentwas made. The tin (II) chelate was 100% effective as a pregnancyterminator but at the high dosage level of 50-100 mg./kg. The copper (I)chelate was 100% effective as a pregnancy terminator at a dosage levelof 10 mg./kg.

Evaluation as Insect Chemosterilant

Unmated housefly adults were held in screen cages with 15 males and 15females in each cage. The compound to be tested as a chemosterilant wasformulated as an emulsion or solution and added to the water source ineach cage at the selected concentration. After four or five days aplastic cup of milk-soaked cotton was pressed against the screen bottomof the cage to serve as an egg-laying substrate. After 48 hours this wasremoved and examined for the presence of eggs. In the case where eggshad been deposited in the plastic cups, these cups were held for 48hours for egg hatch determination. A control group of unmated houseflyadults was kept in separate cages and was not treated with the testcompound. The quantity of eggs laid and the percent hatch are comparedfor the flies treated with selected concentrations of the zinc (II)chelate of 1,1,5,5-tetramethyldithiobiuret and for the control group inthe following Table 1.

                  TABLE 1                                                         ______________________________________                                        Concentration                                                                             Egg Deposited at                                                                             % Egg Hatch                                        ______________________________________                                        0.05%       0              0                                                  0.01%       0              0                                                  0.005%      0              0                                                  Untreated   10             100                                                ______________________________________                                         at Estimated on a 0-10 scale, with 10 being the average for untreated         flies.                                                                   

Evaluation as Inhibitor of Metamorphosis of Insects

Ten larvae of the yellow fever mosquito in the fourth and last larvalinstar were placed in solutions, suspensions or emulsions containingchosen concentrations of the compound under test. The mosquitoes wereheld through the pupal and adult stages to determine the mortalities ofpupae and partially emerged adults. The results when the larvae weretreated with the specified concentrations of the zinc (II) chelate of1,1,5,5 -tetramethyldithiobiuret are shown in the following Table 2.

                  TABLE 2                                                         ______________________________________                                        Concen-                                                                       tration   Number    % Dead   % Dead % Normal                                  (in ppm)  Treated   Larvae   Pupa   Adults                                    ______________________________________                                        5         10        100       0      0                                        0.5       ↓  40       50     10                                        0.25      ↓  30       30     40                                        0.1       ↓   0       40     60                                        ______________________________________                                    

Evaluation as Plant Defoliant

The test compounds were formulated with 4.0% of a surfactant, (a blendof polyoxyethylene (20%) sorbitan monooleate in which the oxyethylenecontent is about 20 mole percent, with mono- and di-glycerides offat-forming fatty acids and an antioxidant mixture), 5% cyclohexanone,15% acetone and water and sprayed at the rates indicated in thefollowing Table 3 on four-week old cotton plants. Ten days aftertreatment a count is made of the number of abcissed and desiccatedleaves on each plant. The percent leaf abscission and/or desiccation wascalculated for each plant. The compounds tested were (A) the zinc (II)chelate of 1,1,5,5-tetramethyldithiobiuret of this invention and (B)3,5-bis(dimethylamino)1,2,4-dithiazolium chloride of U.S. Pat. No.3,166,564. The results are shown in the following Table 3.

                  TABLE 3                                                         ______________________________________                                                 Rate     %           % Desi-                                                  (lb./A)  Abscission  ccation                                         ______________________________________                                        Compound A 1.25       35          35                                                     2.5        52          22                                                     5.0        56          28                                                     10.0       54          26                                          Compound B 1.25       70          11                                                     2.5        76          16                                                     5.0        77          16                                                     10.0       93           7                                          ______________________________________                                    

To use the compounds of this invention as population control agents formammals, including humans, they generally are administered incombination with conventional liquid or solid vehicles to provideelixirs, suspensions, tablets, capsules, powders and the like, accordingto conventional pharmaceutical practice.

Other features, advantages and specific embodiments of this inventionwill become readily apparent to those exercising oridinary skill in theart after reading the foregoing disclosures. Such specific embodimentsare within the scope of the claimed subject matter unless expresslyindicated to the contrary by claim language. Moreover, while specificembodiments of this invention have been described in considerabledetail, variations and modifications of them can be effected withoutdeparting from the spirit and scope of the invention as disclosed andclaimed.

The expression "consisting essentially of" as used in this specificationexcludes any unrecited substance at a concentration sufficient tosubstantially adversely affect the essential properties andcharacteristics of the composition being defined, while permitting thepresence of one or more unrecited substances at concentrationsinsufficient to substantially adversely affect said essential propertiesand characteristics.

What I claim and desire to protect by letters Patent is:
 1. A metal saltof a 1,1,5,5-tetrasubstituted dithiobiuret of the formula: ##EQU12## inwhich R¹, R², R³ and R⁴ independently of each other are selected fromthe group consisting of C₁ -C₁₈ alkyl, C₆ -C₁₂ aryl, C₃ -C₁₂ cycloalkyland these radicals substituted by at least one member of the groupconsisting of hydroxyl, C₁ -C₄ alkyl, C₁ -C₈ aryl, halo and nitro.
 2. Acompound according to claim 1 in which R¹, R², R³ and R⁴ are eachmethyl, and the metal of said metal salt is selected from the groupconsisting of the alkali metals, the alkaline earth metals, zinc,cadmium, tin, mercury, copper, nickel, chromium, iron, silver,manganese, and beryllium.
 3. A compound according to claim 1 in whichR¹, R², R³ and R⁴ are each ethyl.
 4. A compound according to claim 1 inwhich the metal is zinc.
 5. A compound according to claim 1 in which themetal is sodium.
 6. A compound according to claim 1 in which the metalis copper.
 7. The zinc salt of 1,1,5,5-tetramethyldithiobiuret.